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Information on EC 4.3.99.4 - choline trimethylamine-lyase
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4.3.99.4 choline trimethylamine-lyaseIUBMB Comments
The enzyme utilizes a glycine radical to break the C-N bond in choline. Found in choline-degrading anaerobic bacteria.
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Word Map
- 4.3.99.4
- toluene
- p-cresol
- formate-lyase
-
thiyl
- 4-hydroxyphenylacetate
- aromatica
- thauera
-
r-benzylsuccinate
-
radical-based
The expected taxonomic range for this enzyme is: Bacteria, Archaea
Synonyms
glycyl radical enzyme, choline tma-lyase, choline trimethylamine-lyase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
choline TMA-lyase
cutC
Dde_3282
glycyl radical enzyme
glycyl radical enzyme
Oleidesulfovibrio alaskensis G20
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
choline = trimethylamine + acetaldehyde
-
-
-
-
choline = trimethylamine + acetaldehyde
radical reaction or rearrangement mechanism, overview
Oleidesulfovibrio alaskensis
-
choline = trimethylamine + acetaldehyde
radical reaction or rearrangement mechanism, overview
Oleidesulfovibrio alaskensis G20
-
-
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SYSTEMATIC NAME
IUBMB Comments
choline trimethylamine-lyase (acetaldehyde-forming)
The enzyme utilizes a glycine radical to break the C-N bond in choline. Found in choline-degrading anaerobic bacteria.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
choline
trimethylamine + acetaldehyde
-
a glycyl radical-based mechanism of C-N cleavage
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis
-
a glycyl radical-based mechanism of C-N cleavage
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis
-
the enzyme shows strict specificity for choline
-
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis
important route for the production of trimethylamine
-
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis G20
-
the enzyme shows strict specificity for choline
-
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis G20
important route for the production of trimethylamine
-
-
?
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis G20
-
a glycyl radical-based mechanism of C-N cleavage
-
?
additional information
?
-
Oleidesulfovibrio alaskensis
-
the enzyme CutC is a C-N bond-cleaving glycyl radical enzyme
-
-
?
additional information
?
-
Oleidesulfovibrio alaskensis G20
-
the enzyme CutC is a C-N bond-cleaving glycyl radical enzyme
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
choline
trimethylamine + acetaldehyde
Oleidesulfovibrio alaskensis
important route for the production of trimethylamine
-
-
?
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
GRE activating protein
Oleidesulfovibrio alaskensis
-
i.e. CutD, biochemical function of CutD as a glycyl radical enzyme or CutC activase
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Dehydration
Characterization of 1,2-Propanediol Dehydratases Reveals Distinct Mechanisms for B
Heart Diseases
Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3025
choline
Oleidesulfovibrio alaskensis
-
recombinant enzyme, pH 8.0, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
747
choline
Oleidesulfovibrio alaskensis
-
calculated from the EPR activation measurement, recombinant enzyme, pH 8.0, temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22.7
Oleidesulfovibrio alaskensis
-
purified recombinant enzyme, pH 8.0, temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Oleidesulfovibrio alaskensis
Oleidesulfovibrio alaskensis G20
Oleidesulfovibrio alaskensis
member of the glycyl radical enzyme family
UniProt
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
additional information
evolution
Oleidesulfovibrio alaskensis
-
choline TMA-lyase belongs to the glycyl radical enzymes (GREs) utilize protein-based radical intermediates to catalyze a variety of reactions, including nucleotide reduction (class III ribonucleotide reductase (RNR)), C-C bond formation (benzylsuccinate synthase (BSS)), C-C bond cleavage (pyruvate formate-lyase (PFL) and 4-hydroxyphenylacetate decarboxylase (4-HPAD)), and dehydration (B12-independent glycerol dehydratase (GDH))
evolution
Oleidesulfovibrio alaskensis G20
-
choline TMA-lyase belongs to the glycyl radical enzymes (GREs) utilize protein-based radical intermediates to catalyze a variety of reactions, including nucleotide reduction (class III ribonucleotide reductase (RNR)), C-C bond formation (benzylsuccinate synthase (BSS)), C-C bond cleavage (pyruvate formate-lyase (PFL) and 4-hydroxyphenylacetate decarboxylase (4-HPAD)), and dehydration (B12-independent glycerol dehydratase (GDH))
-
metabolism
Oleidesulfovibrio alaskensis
-
the enzyme is involved in anaerobic choline metabolism and encoded in the choline utilization (cut) gene cluster
metabolism
Oleidesulfovibrio alaskensis G20
-
the enzyme is involved in anaerobic choline metabolism and encoded in the choline utilization (cut) gene cluster
-
physiological function
Oleidesulfovibrio alaskensis
gene disruption impairs growth on choline and abolishes production of trimethylamine, with no difference in growth between wild-type and mutant in media containing lactate. Expression of choline trimethylamine-lyase CutC and its activating protein CutD in Escherichia coli BL21 results in production of d9-TMA from (trimethyl-d9)-choline. Expression of either enzyme on its own completely abolishes trimethylamine production
physiological function
Oleidesulfovibrio alaskensis G20
-
gene disruption impairs growth on choline and abolishes production of trimethylamine, with no difference in growth between wild-type and mutant in media containing lactate. Expression of choline trimethylamine-lyase CutC and its activating protein CutD in Escherichia coli BL21 results in production of d9-TMA from (trimethyl-d9)-choline. Expression of either enzyme on its own completely abolishes trimethylamine production
-
additional information
Oleidesulfovibrio alaskensis
-
enzyme homology modeling, docking of choline in the active site of a the enzyme, docking model, overview
additional information
Oleidesulfovibrio alaskensis G20
-
enzyme homology modeling, docking of choline in the active site of a the enzyme, docking model, overview
-
Show AA Sequence and Transmembrane Helices (684 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
124000
mass spectrometry analysis. The 124-kDa full-length CutC protein is very unstable, with the N-terminal part starting to degrade almost immediately after purification by nickel affinity chromatography
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
homodimer
Oleidesulfovibrio alaskensis
-
dimeric oligomerization state for full-length CutC and all of the variants
homodimer
Oleidesulfovibrio alaskensis G20
-
dimeric oligomerization state for full-length CutC and all of the variants
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop method, crystal structures of both the choline-bound and choline free forms of CutC are determined, binding of choline at the ligand-binding site triggers conformational changes in the enzyme structure. Choline-bound CutC crystals exhibit an orthorhombic lattice and space group P212121 with 8 molecules in the asymmetric unit. CutC crystals without choline exhibited a monoclinic lattice and space group P21 with 4 molecules in the asymmetric unit
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T502A
Oleidesulfovibrio alaskensis
turnover number for choline is 4400fold lower than for wild-type enzyme
Y208F
Oleidesulfovibrio alaskensis
turnover number for choline is 215fold lower than for wild-type enzyme
Y208F/Y506F
Oleidesulfovibrio alaskensis
turnover number for choline is 1050fold lower than for wild-type enzyme
Y506F
Oleidesulfovibrio alaskensis
turnover number for choline is 48fold lower than for wild-type enzyme
C489A
Oleidesulfovibrio alaskensis G20
-
complete loss of activity
-
E491A
Oleidesulfovibrio alaskensis G20
-
no activity detectable
-
E491Q
Oleidesulfovibrio alaskensis G20
-
no activity detectable
-
G821A
Oleidesulfovibrio alaskensis G20
-
complete loss of activity
-
T334S
Oleidesulfovibrio alaskensis G20
-
site-directed mutagenesis, the mutant retains activity
-
T502A
Oleidesulfovibrio alaskensis G20
-
turnover number for choline is 4400fold lower than for wild-type enzyme
-
T502S
Oleidesulfovibrio alaskensis G20
-
site-directed mutagenesis, the mutant retains activity
-
Y208F
Oleidesulfovibrio alaskensis G20
-
turnover number for choline is 215fold lower than for wild-type enzyme
-
Y506F
Oleidesulfovibrio alaskensis G20
-
turnover number for choline is 48fold lower than for wild-type enzyme
-
additional information
additional information
Oleidesulfovibrio alaskensis
-
condtruction of a -52 amino acid truncated variant, removal of the predicted N-terminal microcompartment targeting sequence from CutC improves yields and solubility without impacting activity
additional information
Oleidesulfovibrio alaskensis G20
-
condtruction of a -52 amino acid truncated variant, removal of the predicted N-terminal microcompartment targeting sequence from CutC improves yields and solubility without impacting activity
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His6-tagged wild-type and point and N-terminal truncation mutant enzymes from Escherichia coli
Oleidesulfovibrio alaskensis
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene cutC, cloning and overexpression of the N-terminally His6-tagged wild-type and point and N-terminal truncation mutant enzymes in Escherichia coli
Oleidesulfovibrio alaskensis
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Craciun, S.; Balskus, E.P.
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
Proc. Natl. Acad. Sci. USA
109
21307-21312
2012
Desulfovibrio desulfuricans, Desulfovibrio desulfuricans (B8J0I2), Oleidesulfovibrio alaskensis (Q30W70), Oleidesulfovibrio alaskensis G20 (Q30W70)
brenda
Craciun, S.; Marks, J.A.; Balskus, E.P.
Characterization of choline trimethylamine-lyase expands the chemistry of glycyl radical enzymes
ACS Chem. Biol.
9
1408-1413
2014
Oleidesulfovibrio alaskensis, Oleidesulfovibrio alaskensis G20
brenda
Bodea, S.; Funk, M.A.; Balskus, E.P.; Drennan, C.L.
Molecular basis of C-N bond cleavage by the glycyl radical enzyme choline trimethylamine-lyase
Cell Chem. Biol.
23
1206-1216
2016
Oleidesulfovibrio alaskensis (Q30W70), Oleidesulfovibrio alaskensis G20 (Q30W70)
brenda
Kalnins, G.; Kuka, J.; Grinberga, S.; Makrecka-Kuka, M.; Liepinsh, E.; Dambrova, M.; Tars, K.
Structure and function of CutC choline lyase from human microbiota bacterium Klebsiella pneumoniae
J. Biol. Chem.
290
21732-21740
2015
Klebsiella pneumoniae (A0A0M3KL45), Klebsiella pneumoniae
brenda
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